Cai Weijie, Li Ping, Gu Mingxue, Xu Haoxing
Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China.
Department of Molecular and Human Genetics, Baylor College of Medicine, Jan and Dun Neurological Research Institute, Houston, TX, USA.
Handb Exp Pharmacol. 2023;278:93-108. doi: 10.1007/164_2023_640.
Intracellular organelles exchange their luminal contents with each other via both vesicular and non-vesicular mechanisms. By forming membrane contact sites (MCSs) with ER and mitochondria, lysosomes mediate bidirectional transport of metabolites and ions between lysosomes and organelles that regulate lysosomal physiology, movement, membrane remodeling, and membrane repair. In this chapter, we will first summarize the current knowledge of lysosomal ion channels and then discuss the molecular and physiological mechanisms that regulate lysosome-organelle MCS formation and dynamics. We will also discuss the roles of lysosome-ER and lysosome-mitochondria MCSs in signal transduction, lipid transport, Ca transfer, membrane trafficking, and membrane repair, as well as their roles in lysosome-related pathologies.
细胞内细胞器通过囊泡和非囊泡机制相互交换其腔内容物。通过与内质网和线粒体形成膜接触位点(MCSs),溶酶体介导代谢物和离子在溶酶体与调节溶酶体生理、运动、膜重塑和膜修复的细胞器之间的双向运输。在本章中,我们将首先总结溶酶体离子通道的现有知识,然后讨论调节溶酶体 - 细胞器MCS形成和动态变化的分子和生理机制。我们还将讨论溶酶体 - 内质网和溶酶体 - 线粒体MCS在信号转导、脂质运输、钙转运、膜运输和膜修复中的作用,以及它们在溶酶体相关病理中的作用。